Cutaneous lupus erythematosus induced by golimumab therapy.

Abstract

Dear Editor, We would like to report the case of our patient who is a 63-year-old Arab woman of Omani origin who had rheumatoid arthritis (RA) for more than 10 years. She was seropositive for both rheumatoid factor and anticyclic citrullinated peptide antibody (anti-CCP). She also had sicca symptoms in the form of dry eyes and dry mouth with positive anti-Ro/Sjögren's syndrome A (SSA) antibody but had negative anti-nuclear antibody (ANA) serology. Her arthritis was severe enough so as to need bilateral knee joint and right hip joint total replacement surgeries. She received disease-modifying anti-rheumatic drug (DMARD) therapy previously in the form of oral methotrexate (MTX) for around 6 months, to which she was intolerant due to marked dyspepsia and thus was discontinued, later was lost for follow-up as she was rather uncompliant with medications and with attendance for follow-up visits. In addition, she had other co-morbidities including hypertension and ischemic heart disease. Later she was admitted to the medical ward with severe flare of polyarthritis involving shoulders, wrists and hands. Laboratory investigations revealed a grossly raised erythrocyte sedimentation rate (ESR) at 136 mm/h, C-reactive protein (CRP) of 97 mg/L (normal < 5 mg/L) with normochromic normocytic anemia Hemoglobin OF 8.9 gm/dl. Her Disease Activity Score of 28 joints (DAS28) was recorded as 7.1 X-rays of the dorsolumbar spine revealed multiple vertebral bodies height reduction with pencil-drawn vertebrae appearance in favor of osteoporosis and that was confirmed with a dual-energy X-ray absorptiometry (DEXA) scan revealing a bone density in the osteoporotic range. Her shoulder arthritis responded extremely well to intra-articular steroids injections. DMARD therapy was initiated in the form of leflunomide tablets (LEF) 20 mg per day for 12 weeks but with only marginal benefit. It was noted that the patient developed anorexia with weight loss assumed to be an adverse effects to LEF, thus the dose was reduced to 10 mg once daily. Being a non-biologic, DMARDs inadequate responders, thus biologics therapeutic options were discussed with the patient and accordingly she was started on anti-tumor necrosis factor (anti-TNF) therapy in the form of monthly golimumab 50 mg subcutaneously, also receiving on the same day intravenous infusion of zoledronic acid 5 mg for the underlying osteoporosis. She responded quite well to this therapy with marked subjective and clinical improvement of her arthritis. She received the second dose of golimumab 1 month later; however, almost 3 weeks after that injection, she presented to the dermatologist with extensive rash in the form of annular erythematous scaly psoriasiform eruption on the chest, upper back and arms consistent with subacute cutaneous lupus. The scalp and ears showed atrophic patches with scaling and dyspigmentation, follicular plugging and cicatritial alopecia consistent with discoid lupus erythematosus (Figs 1, 2). Skin biopsy from the lesions in the upper back showed on histopathology a basket weave hyperkeratosis and follicular plugging. Interface changes were characterized by basal vacuolization and pigment incontinence. Within the dermis, there were superficial perivascular and perifollicular lymphocytic infiltrates and dermal edema suggestive of mucin (Fig. 3). The use of protein-based anti-TNF-α therapies such as antibodies and soluble TNF-α receptors is commonly associated with the induction of autoantibodies, whereas anti-TNF-induced lupus (ATIL) is rare.1 ATIL can occur with any of the available TNF inhibitors, but the frequency and clinical characteristics of ATIL vary between different drugs. Cutaneous, renal and cerebral involvements as well as double-stranded DNA antibodies are more common in ATIL compared to classic drug-induced lupus (DIL), suggesting different pathogenic mechanisms of ATIL and DIL. The pathogenesis of ATIL is still unknown. Concomitant immunosuppression can reduce autoantibody formation in ATIL, and withdrawal of anti-TNF-α therapy usually leads to resolution of symptoms.2 Chronic discoid lupus erythematosus is characterized by erythema, scaling, atrophy and dyspigmentation in addition to scarring, most often affecting the face, scalp and ears. Individual cases of TNF inhibitor-induced discoid lupus have been reported.3 Subacute cutaneous lupus erythematosus (SCLE) is characterized by photodistributed, nonscarring, annular or papulosquamous lesions. Our case showed overlap features of both chronic discoid LE and SCLE. SCLE patients usually have elevated anti-Ro/SSA antibodies. Roughly 15%–20% of patients with new-onset SCLE are associated with the ‘recent’ introduction of a drug. The clinical, histopathologic and serologic features of patients with drug-induced SCLE (DI-SCLE) do not differ from those seen in patients with idiopathic disease. DI-SCLE has been reported with etanercept, adalimumab and infliximab.4 Only two cases have been reported in the literature in which golimumab has induced SCLE reaction.5, 6 Golimumab should be added to the list of medications capable of inducing or exacerbating cutaneous lupus erythematosus. Our patient is a clear example of an such adverse event, although she was lost for follow-up so we were unable to trace her clinical and serological progress.